Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells.
During persistent murine cytomegalovirus (MCMV) infection, the T cell response is maintained at extremely high intensity for the life of the host. These cells closely resemble human CMV-specific cells, which compose a major component of the peripheral T cell compartment in most people. Despite a phenotype that suggests extensive antigen-driven differentiation, MCMV-specific T cells remain functional and respond vigorously to viral challenge. We hypothesized that a low rate of antigen-driven proliferation would account for the maintenance of this population. Instead, we found that most of these cells divided only sporadically in chronically infected hosts and had a short half-life in circulation. The overall population was supported, at least in part, by memory T cells primed early in infection, as well as by recruitment of naive T cells at late times. Thus, these data show that memory inflation is maintained by a continuous replacement of short-lived, functional cells during chronic MCMV infection.
Snyder
Christopher M
CM
Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, OR 97239, USA. snydechr@ohsu.edu
Cho
Kathy S
KS
Bonnett
Elizabeth L
EL
van Dommelen
Serani
S
Shellam
Geoffrey R
GR
Hill
Ann B
AB
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D006566:Herpesviridae Infections / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism